Three patients with fever and rash after a stay in Morocco: infection with Rickettsia conorii

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1 Three patients with fever and rash after a stay in Morocco: infection with Rickettsia conorii Stylemans D 1, Mertens R 1, Seyler L 1, Piérard D 2, Lacor P 1 1. Department of Internal Medicine, UZ Brussel 2. Department of Microbiology and Hospital Hygiene, UZ Brussel 12/01/2017 1

2 Content Rickettsia conorii Case reports Conclusion and take home messages Questions and answers References 21th annual congress of the BSIM 12/01/2017 2

3 Rickettsia conorii Mediterranean spotted fever Rickettsia spp. spotted fever group 4 different subtypes R. conorii R. conorii caspia R. conorii israelensis R. conorii indica Rhipicefalus sanguineus: brown dog tick Champman AS et al. MMWR Recomm Rep 2006; 55 (RR-4):1. 21th annual congress of the BSIM 12/01/2017 3

Plos Negl Trop 2008; 2 (11): e338. Rovery C.

4 Rickettsia conorii - epidemiology Rickettsia species Rickettsia conorii Parola P. et al. Warmer weather linked to tick attack and emergence of severe ricketssioses. Plos Negl Trop 2008; 2 (11): e338. Rovery C. Questions on Mediterranean spotted fever a century after its discovery. Emerg Infect Dis 2008; 14(9): 1360)7. 21th annual congress of the BSIM 12/01/2017 4

5 Case 1 62 year old male Hypercholesterolemia: R/simvastatin 20 mg Recent 4 week stay in Morocco (july august 2016) Symptomatology: black necrotic scabbed skin lesion generalized myalgia and fever (39,5 C) generalized maculopapular rash 21th annual congress of the BSIM 12/01/2017 5

6 Case 1: tache noire 21th annual congress of the BSIM 12/01/2017 6

7 Case 1: maculopapular rash 21th annual congress of the BSIM 12/01/2017 7

8 Symptomatology of Rickettsia conorii Incubation time: 5-7 days acute onset Fever (94-100%) Rash (87-96%): maculopapular or petechial Flu-like symptoms (78%) Tache noire (53-77%) Parola P et al. Update on tick-borne ricketssioses around the world: a geographic approach. Clin Microbiol Rev 2013, 26(4): th annual congress of the BSIM 12/01/2017 8

9 Case 1: lab results (1) Parameter Value SI Sodium 127 mmol/l Chloride 92 mmol/l CRP 61,6 mg/dl LDH 657 U/L AST 86 U/L ALT 98 U/L AP 131 U/L γgt 488 U/L Thrombocytes 152 /mm³ White blood cells 7,1 X 10³/mm³ 21th annual congress of the BSIM 12/01/2017 9

10 Case 1: lab results (2) Negative blood cultures Serology: Micro-organism IgM IgG Hepatitis A virus - + Hepatitis C virus - + EBV - CMV - + Rickettsia conorii 1/512 Biopsy tache noire: positive PCR for Rickettsia conorii 21th annual congress of the BSIM 12/01/

11 Case 1: treatment Doxycycline 200mg/d 21th annual congress of the BSIM 12/01/

12 Case 2 66 year old male Medical history: diabetes mellitus type 2: R/metformin gastritis: R/pantoprazol splenectomy (post trauma) appendectomy osteosynthesis left shoulder Recent stay for 4 months in Morocco (May August 2016) 21th annual congress of the BSIM 12/01/

13 Case 2 Symptomatology fever (39,5 C) headache generalized myalgia R/amoxicillin-clavulanate 2 days maculopapular rash Initial differential at E.D.: meningitis- encephalitis pneumococcal sepsis Mediterranean spotted fever 21th annual congress of the BSIM 12/01/

14 Case 2: lab results (1) Parameter Value SI Sodium 132 mmol/l Chloride 94 mmol/l CRP 241,8 mg/dl LDH 806 U/L AST 92 U/L ALT 49 U/L AP 118 U/L γgt 147 U/L Thrombocytes 117 /mm³ White blood cells 10,5 X 10³/mm³ 21th annual congress of the BSIM 12/01/

15 Case 2: lab results (2) Normal CSF analysis Normal CT brain CT thorax: COPD configuration, chronic bronchitis Negative blood cultures Serology: Micro-organism IgM IgG EBV - CMV - + Rickettsia conorii 1/512 Rickettsia conorii (1m) 1/ th annual congress of the BSIM 12/01/

16 Case 2: treatment Initially ceftriaxone IV After 2 days: doxycycline 200 mg/d 21th annual congress of the BSIM 12/01/

17 Meningoencefalitis in MSF Case reports: meningitis-encephalitis-myelitis Aliaga L et al. Mediterranean spotted fever with encephalitis. J Med Microbiol 2009; 58 (4): th annual congress of the BSIM 12/01/

18 Case 3 59 year old woman Diabetes mellitus type 2: R/metformin Recent stay in Morocco (May July 2016) Symptomatology: fever - generalized myalgia (present in Morocco since 4 days) maculopapular rash 21th annual congress of the BSIM 12/01/

19 Rash and tache noire 21th annual congress of the BSIM 12/01/

20 Case 3: lab results Parameter Value SI Sodium 131 mmol/l Chloride 92 mmol/l CRP 264,7 mg/dl LDH 1087 U/L AST 127 U/L ALT 169 U/L AP 80 U/L γgt 63 U/L Thrombocytes 155 /mm³ White blood cells 5,0 X 10³/mm³ 21th annual congress of the BSIM 12/01/

21 Case 3: treatment R/amoxicillin-clavulanate (empirically) After physical examination at internal medicine ward switched to doxycyclin 200mg/d Serology R. conorii initially negative Control sample running 21th annual congress of the BSIM 12/01/

22 Case 3: evolution CRP - AST 21th annual congress of the BSIM 12/01/

23 Conclusion and take home messages Include Mediterranean spotted fever fever maculopapular rash recent stay in endemic region Tache noire = pathognomonic Serology + PCR biopsy Treatment of choice : doxycycline 21th annual congress of the BSIM 12/01/

24 Questions and answers Thank you all for listening. Questions? 21th annual congress of the BSIM 12/01/

25 References (1) Champman, AS, Bakken, JS, Folk, SM, et al. Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain Spotted Fever, Ehrlichoioses, and Anaplasmosis-United States: A practical guide for physicians and other health-care and public health professionals. MMWR Recomm Rep 2006; 55(RR-4):1. Portillo A et al. Ricketssiosis in Europe. Microbes Infect 2015; 17 (11-12): Sexton DJ, McClain MT. Other spotted fever group rickettsial infections. Uptodate 2016: (accessed november 26th 2016). Sexton DJ, McClain MT. Clinical manifestiations and diagnosis of Rocky Mountain Spotted Fever. Uptodate 2016: (accessed november 26th 2016). Zhu Y et al. Proposal to create subspecies of Rickettsia conorii based on multi-locus sequence typing and an emended description of Rickettsia conorii. BMC Microbiol 2005; 5:11. Parola P. et al. Warmer weather linked to tick attack and emergence of severe ricketssioses. Plos Negl Trop 2008; 2 (11): e338. Rovery C. Questions on Mediterranean spotted fever a century after its discovery. Emerg Infect Dis 2008; 14(9): 1360)7. Parola P et al. Update on tick-borne ricketssioses around the world: a geographic approach. Clin Microbiol Rev 2013, 26(4): th annual congress of the BSIM 12/01/

26 References (2) Delord M et al. Rickettsioses and Q fever in travelers ( ). Travel Med Infect Dis. 2014; 12(5): Aliaga L et al. Mediterranean spotted fever with encephalitis. J Med Microbiol 2009; 58 (4): Duque et al. Mediterranean spotted fever and encephalitis: a case report and review of the literature. J Infect Chemother 2012; 18(1): Brouqui P et al. Guidelines for the diagnosis of tick-borne bacterial disease in Europe. Clin Microbiol Infect 2004; 10(12): th annual congress of the BSIM 12/01/

Box 4. Mediterranean Spotted Fever (* controversial result due to the possibility of cross-reaction with other Rickettsia species).

Box 4. Mediterranean Spotted Fever (* controversial result due to the possibility of cross-reaction with other Rickettsia species). Mediterranean spotted fever Mediterranean spotted fever (MSF) (or Boutonneuse fever, or Marseilles fever) is a Mediterranean endemic tick-borne disease belonging to the rickettsiosis group (Box 4), the